Publications by authors named "Zhang Cui"

297 Publications

Inhibition of MIR4435-2HG on Invasion, Migration, and EMT of Gastric Carcinoma Cells by Mediating MiR-138-5p/Sox4 Axis.

Front Oncol 2021 31;11:661288. Epub 2021 Aug 31.

The Second Department of General Surgery, Cangzhou Central Hospital, Cangzhou, China.

Background: The previous investigations have identified that long non-coding RNA (lncRNAs) act as crucial regulators in gastric carcinoma. However, the function of lncRNA MIR4435-2HG in the modulation of gastric carcinoma remains elusive. Here, we aimed to explore the role of MIR4435-2HG in gastric carcinoma.

Method: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were applied to select the differently expressed lncRNAs in gastric carcinoma. The qRT-PCR was applied to analyze MIR4435-2HG expression in carcinoma tissues and cell lines. The effect of MIR4435-2HG on proliferation, invasion, migration, and apoptosis of gastric carcinoma cells was detected by Cell Counting Kit-8 (CCK-8) assays, transwell assays, and flow cytometry . A subcutaneous tumor model was constructed to examine the tumor growth of gastric carcinoma cells after knocking out MIR4435-2HG. RNA immunoprecipitation and luciferase reporting assays were applied to evaluate the interaction of MIR4435-2HG, miR-138-5p, and Sox4.

Results: The bioinformatics analysis based on TCGA and GEO databases indicated that MIR4435-2HG was obviously elevated in gastric carcinoma samples. The qRT-PCR analysis revealed that MIR4435-2HG was upregulated in clinical gastric carcinoma tissues and cells. The high expression of MIR4435-2HG is associated with the poor survival rate of patients. The knockout of MIR4435-2HG could repress the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) and accelerate the apoptosis of gastric carcinoma cells. Moreover, the deletion of MIR4435-2HG was able to attenuate the tumor growth . Mechanically, we identified that MIR4435-2HG enhanced Sox4 expression by directly interacting with miR-138-5p as a competitive endogenous RNA (ceRNA) in gastric carcinoma cells, in which Sox4 was targeted by miR-138-5p.

Conclusion: MIR4435-2HG is elevated in gastric carcinoma cells and contributes to the growth, metastasis, and EMT of gastric carcinoma cells by targeting miR-138-5p/Sox4 axis. MIR4435-2HG may be applied as a potential therapeutic target in gastric carcinoma.
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http://dx.doi.org/10.3389/fonc.2021.661288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438303PMC
August 2021

Effects of Eight Methods and Five Steps of Tai Chi Practice on Balance Control Among Older Adults.

Motor Control 2021 Sep 16:1-15. Epub 2021 Sep 16.

College of Sports and Health, Shandong Sport University, Jinan, Shandong,China.

The team developed the newly compiled eight methods and five steps of Tai Chi (EMFSTC), which includes introductory routines to Tai Chi characterized by simple structures. This study examined the effectiveness of EMFSTC practice on balance control. A total of 31 participants were randomly assigned to EMFSTC (n = 15, age = 66.4 ± 1.7 years, received 16-week EMFSTC practice) or control (n = 16, age = 66.7 ± 1.8 years, received no practice) groups. Significant group by training interactions were observed. After EMFSTC practice, balance control improved, as indicated by decreased root mean square and mean velocity of center of pressure, proprioception threshold during knee extension, and plantar tactile sensitivity threshold at the arch. EMFSCT can be an effective rehabilitation modality to improve balance control among older adults.
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http://dx.doi.org/10.1123/mc.2021-0022DOI Listing
September 2021

Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease.

Gut Microbes 2021 Jan-Dec;13(1):1968257

Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Host-microbial cross-talk plays a crucial role in maintenance of gut homeostasis. However, how microbiota-derived metabolites, e.g., butyrate, regulate functions of neutrophils in the pathogenesis of inflammatory bowel disease (IBD) remains elusive. We sought to investigate the effects of butyrate on IBD neutrophils and elucidate the therapeutic potential in regulating mucosal inflammation. Peripheral neutrophils were isolated from IBD patients and healthy donors, and profiles of proinflammatory cytokines and chemokines were determined by qRT-PCR and ELISA, respectively. The migration and release of neutrophil extracellular traps (NETs) were studied by a Transwell model and immunofluorescence, respectively. The role of butyrate in regulating IBD neutrophils was evaluated in a DSS-induced colitis model in mice. We found that butyrate significantly inhibited IBD neutrophils to produce proinflammatory cytokines, chemokines, and calprotectins. Blockade of GPCR signaling with pertussis toxin (PTX) did not interfere the effects whereas pan-histone deacetylase (HDAC) inhibitor, trichostatin A (TSA) effectively mimicked the role of butyrate. Furthermore, studies confirmed that butyrate suppressed neutrophil migration and formation of NETs from both CD and UC patients. RNA sequencing analysis revealed that the immunomodulatory effects of butyrate on IBD neutrophils were involved in leukocyte activation, regulation of innate immune response and response to oxidative stress. Consistently, oral administration of butyrate markedly ameliorated mucosal inflammation in DSS-induced murine colitis through inhibition of neutrophil-associated immune responses such as proinflammatory mediators and NET formation. Our data thus reveal that butyrate constrains neutrophil functions and may serve as a novel therapeutic potential in the treatment of IBD.
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http://dx.doi.org/10.1080/19490976.2021.1968257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437544PMC
September 2021

Pinocembrin ameliorates post-infarct heart failure through activation of Nrf2/HO-1 signaling pathway.

Mol Med 2021 09 6;27(1):100. Epub 2021 Sep 6.

Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, Hubei, People's Republic of China.

Background: Oxidative stress is an important factor involved in the progress of heart failure. The current study was performed to investigate whether pinocembrin was able to ameliorate post-infarct heart failure (PIHF) and the underlying mechanisms.

Methods: Rats were carried out left anterior descending artery ligation to induce myocardial infarction and subsequently raised for 6 weeks to produce chronic heart failure. Then pinocembrin was administrated every other day for 2 weeks. The effects were evaluated by echocardiography, western blot, Masson's staining, biochemical examinations, immunohistochemistry, and fluorescence. In vitro we also cultured H9c2 cardiomyocytes and cardiac myofibroblasts to further testify the mechanisms.

Results: We found that PIHF-induced deteriorations of cardiac functions were significantly ameliorated by administrating pinocembrin. In addition, the pinocembrin treatment also attenuated collagen deposition and augmented vascular endothelial growth factor receptor 2 in infarct border zone along with an attenuated apoptosis, which were related to an amelioration of oxidative stress evidenced by reduction of reactive oxygen species (ROS) in heart tissue and malondialdehyde (MDA) in serum, and increase of superoxide dismutase (SOD). This were accompanied by upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway. In vitro experiments we found that specific Nrf2 inhibitor significantly reversed the effects resulted from pinocembrin including antioxidant, anti-apoptosis, anti-fibrosis and neovascularization, which further indicated the amelioration of PIHF by pinocembrin was in a Nrf2/HO-1 pathway-dependent manner.

Conclusion: Pinocembrin ameliorated cardiac functions and remodeling resulted from PIHF by ROS scavenging and Nrf2/HO-1 pathway activation which further attenuated collagen fibers deposition and apoptosis, and facilitated angiogenesis.
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http://dx.doi.org/10.1186/s10020-021-00363-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422663PMC
September 2021

microRNA-4429-5p suppresses the malignant development of colon cancer by targeting matrix metalloproteinase 16.

In Vitro Cell Dev Biol Anim 2021 Aug 26;57(7):715-725. Epub 2021 Aug 26.

The Second Department of General Surgery, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, China.

Colon cancer has been recognized as the major reason for global cancer-associated mortality. microRNA (miRNA, miR)-4429-5p has been documented to act as a tumor-suppressive miRNA in some cancers, but its effect on colon cancer remains elusive. In this study, the biological effects of miR-4429-5p were investigated both in vitro by MTT, 5-ethynyl-2'-deoxyuridine (EdU), wound healing, and transwell assays and in vivo by a xenograft mice model. Western blot, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and dual-luciferase assay were used to identify the binding of miR-4429-5p on matrix metalloproteinase 16 (MMP16) 3'-UTR. Our results suggested that overexpression of miR-4429-5p hindered colon cancer cell proliferation, migration, and invasion, whereas knockdown of miR-4429-5p exhibited the opposite effect in colon cancer cells. Mechanistically, miR-4429-5p directly bound to the 3'-UTR of MMP16 and led to inhibition of MMP16 protein. Overexpression of miR-4429-5p inhibited colon tumor growth by targeting MMP16. Taken together, our study revealed that miR-4429-5p prevented colon cancer progression through targeting MMP16, indicating miR-4429-5p as a promising target for treatment improvement for colon cancer.
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http://dx.doi.org/10.1007/s11626-021-00603-4DOI Listing
August 2021

Salt-inducible kinase 2 regulates energy metabolism in rats with cerebral ischemia-reperfusion.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Jun;50(3):352-360

Clinical Colloge of Wannan Medical College.

To investigate the effects of salt-inducible kinase 2 (SIK2) on energy metabolism in rats with cerebral ischemia-reperfusion. Adult SD male rats were divided into 5 groups: sham group, ischemia group, reperfusion group, adenovirus no-load group, and SIK2 overexpression group with 5 animals in each group. The middle cerebral artery occlusion (MCAO) was induced with the modified Zea-Longa line thrombus method to establish the cerebral ischemia reperfusion model. Eight days before the MCAO, SIK2 overexpression was induced by injecting 7 μL adenovirus in the right ventricle, then MCAO was performed for followed by reperfusion HE staining was used to observe the pathological changes of cerebral tissue in rats; TTC staining was used to observe the volume of cerebral infarct. The levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) in rat brain tissue were detected by ELISA; the levels of SIK2 and hypoxia-inducible factor 1α (HIF-1α) in the rat brain tissues were detected by RT-qPCR and Western blotting. Compared with the sham group, SIK2 level was decreased in the ischemia group, and it was further declined in the reperfusion group (<0.05). Compared with the sham group and ischemic group, the pathological injury in reperfusion group were more severe, and the infarct size was larger; compared with the reperfusion group and adenovirus no-load group, the pathological injury of the SIK2 overexpression group was milder, and the infarct size is less. Compared with the sharn group, HIF-1α was increased in both ischemia group and reperfusion group, especially in ischemia group (all <0.05); HIF-1α level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05). ATP level in ischemia group and reperfusion group was lower than that in the sham group, and the reperfusion group decreased more significantly than the ischemia group (<0.05); ADP content was increased in the ischemia and reperfusion group, and the ADP content in reperfusion group was significantly higher than that in the ischemia group (<0.05). ATP level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05), and ADP was decreased in the SIK2 overexpression group (all <0.05). SIK2 can up-regulate the ATP level and down-regulate the ADP level in rat brain tissue and alleviate cerebral ischemia-reperfusion injury by increase the level of HIF-1α.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0164DOI Listing
June 2021

Conservation of Imprinting and Methylation of , and Genes in Cattle.

Animals (Basel) 2021 Jul 2;11(7). Epub 2021 Jul 2.

College of Life Science, Agricultural University of Hebei, Baoding 071000, China.

Genomic imprinting is the epigenetic mechanism of transcriptional regulation that involves differential DNA methylation modification. Comparative analysis of imprinted genes between species can help us to investigate the biological significance and regulatory mechanisms of genomic imprinting. , and are three maternally imprinted genes identified in the human PWS/AS imprinted locus. This study aimed to assess the allelic expression of , and and to examine the differentially methylated regions (DMRs) of bovine PWS/AS imprinted domains. An expressed single-nucleotide polymorphism (SNP)-based approach was used to investigate the allelic expression of , and genes in bovine adult tissues and placenta. Consistent with the expression in humans and mice, we found that the , and genes exhibit monoallelic expression in bovine somatic tissues and the paternal allele expressed in the bovine placenta. Three DMRs, PWS-IC, and DMR, were identified in the bovine imprinted region by analysis of the DNA methylation status in bovine tissues using the bisulfite sequencing method and were located in the promoter and exon 1 of the gene, promoter and 5' untranslated region (5'UTR) of gene, respectively. The PWS-IC DMR is a primary DMR inherited from the male or female gamete, but and DMR are secondary DMRs that occurred after fertilization by examining the methylation status in gametes.
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http://dx.doi.org/10.3390/ani11071985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300276PMC
July 2021

Foot and Ankle Kinematics During Activities Measured by Using a Dual Fluoroscopic Imaging System: A Narrative Review.

Front Bioeng Biotechnol 2021 19;9:693806. Epub 2021 Jul 19.

School of Kinesiology, Shanghai University of Sport, Shanghai, China.

Foot and ankle joints are complicated anatomical structures that combine the tibiotalar and subtalar joints. They play an extremely important role in walking, running, jumping and other dynamic activities of the human body. The kinematic analysis of the foot and ankle helps deeply understand the movement characteristics of these structures, as well as identify abnormal joint movements and treat related diseases. However, the technical deficiencies of traditional medical imaging methods limit studies on foot and ankle biomechanics. During the last decade, the dual fluoroscopic imaging system (DFIS) has enabled the accurate and noninvasive measurements of the dynamic and static activities in the joints of the body. Thus, this method can be utilised to quantify the movement in the single bones of the foot and ankle and analyse different morphological joints and complex bone positions and movement patterns within these organs. Moreover, it has been widely used in the field of image diagnosis and clinical biomechanics evaluation. The integration of existing single DFIS studies has great methodological reference value for future research on the foot and ankle. Therefore, this review evaluated existing studies that applied DFIS to measure the kinematics of the foot and ankle during various activities in healthy and pathologic populations. The difference between DFIS and traditional biomechanical measurement methods was shown. The advantages and shortcomings of DFIS in practical application were further elucidated, and effective theoretical support and constructive research direction for future studies on the human foot and ankle were provided.
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http://dx.doi.org/10.3389/fbioe.2021.693806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327092PMC
July 2021

Therapeutic Dose of Hydroxyurea-Induced Synaptic Abnormalities on the Mouse Spermatocyte.

Front Physiol 2021 9;12:666339. Epub 2021 Jul 9.

Laboratory of Molecular Cytogenetics, School of Bioengineering, Xuzhou University of Technology, Xuzhou, China.

Hydroxyurea (HU) is a widely used pharmacological therapy for sickle cell disease (SCD). However, replication stress caused by HU has been shown to inhibit premeiotic S-phase DNA, leading to reproductive toxicity in germ cells. In this study, we administered the therapeutic doses of HU (i.e., 25 and 50 mg/kg) to male mice to explore whether replication stress by HU affects pachytene spermatocytes and causes the abnormalities of homologous chromosomes pairing and recombination during prophase I of meiosis. In comparison with the control group, the proportions of spermatocyte gaps were significantly different in the experimental groups injected with 25 mg/kg ( < 0.05) and 50 mg/kg of HU ( < 0.05). Moreover, the proportions of unrepaired double-stranded breaks (DSBs) observed by γH2AX staining also corresponded to a higher HU dose with a greater number of breaks. Additionally, a reduction in the counts of recombination foci on the autosomal SCs was observed in the pachytene spermatocytes. Our results reveal that HU has some effects on synaptonemal complex (SC) formation and DSB repair which suggest possible problems in fertility. Therefore, this study provides new evidence of the mechanisms underlying HU reproductive toxicity.
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http://dx.doi.org/10.3389/fphys.2021.666339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299468PMC
July 2021

Relationship of proprioception, cutaneous sensitivity, and muscle strength with the balance control among older adults.

J Sport Health Sci 2021 Jul 20. Epub 2021 Jul 20.

Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China; Department of Health Sciences and Kinesiology, Georgia Southern University, Statesboro, GA 30460, USA. Electronic address:

Background: Balance impairment is one of the strongest risk factors for falls. Proprioception, cutaneous sensitivity, and muscle strength are 3 important contributors to balance control in older adults. The relationship that dynamic and static balance control has to proprioception, cutaneous sensitivity, and muscle strength is still unclear. This study was performed to investigate the relationship these contributors have to dynamic and static balance control.

Methods: A total of 164 older adults (female = 89, left dominant = 15, age: 73.5 ± 7.8 years, height: 161.6 ± 7.1 cm, weight: 63.7 ± 8.9 kg, mean ± SD) participated in this study. It tested the proprioception of their knee flexion/extension and ankle dorsi/plantarflexion, along with cutaneous sensitivity at the great toe, first and fifth metatarsals, arch, and heel, and the muscle strength of their ankle dorsi/plantarflexion and hip abduction. The Berg Balance Scale (BBS) and the root mean square (RMS) of the center of pressure (CoP) were collected as indications of dynamic and static balance control. A partial correlation was used to determine the relationship between the measured outcomes variables (BBS and CoP-RMS) and the proprioception, cutaneous sensitivity, and muscle strength variables.

Results: Proprioception of ankle plantarflexion (r = -0.306, p = 0.002) and dorsiflexion (r = -0.217, p = 0.030), and muscle strength of ankle plantarflexion (r = 0.275, p = 0.004), dorsiflexion (r = 0.369, p < 0.001), and hip abduction (r = 0.342, p < 0.001) were weakly to moderately correlated with BBS. Proprioception of ankle dorsiflexion (r = 0.218, p = 0.020) and cutaneous sensitivity at the great toe (r = 0.231, p = 0.041) and arch (r = 0.285, p = 0.002) were weakly correlated with CoP-RMS in the anteroposterior direction. Proprioception of ankle dorsiflexion (r = 0.220, p = 0.035), knee flexion (r = 0.308, p = 0.001) and extension (r = 0.193, p = 0.040), and cutaneous sensitivity at the arch (r = 0.206, p = 0.028) were weakly to moderately correlated with CoP-RMS in the mediolateral direction.

Conclusion: There is a weak-to-moderate relationship between proprioception and dynamic and static balance control, a weak relationship between cutaneous sensitivity and static balance control, and a weak-to-moderate relationship between muscle strength and dynamic balance control.
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http://dx.doi.org/10.1016/j.jshs.2021.07.005DOI Listing
July 2021

Nonadiabatic Dynamics of Photocatalytic Water Splitting on A Polymeric Semiconductor.

Nano Lett 2021 Aug 19;21(15):6449-6455. Epub 2021 Jul 19.

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

To elucidate the nature of light-driven photocatalytic water splitting, a polymeric semiconductor-graphitic carbon nitride (g-CN)-has been chosen as a prototype substrate for studying atomistic water spitting processes in realistic environments. Our nonadiabatic quantum dynamics simulations based on real-time time-dependent density functional theory reveal explicitly the transport channel of photogenerated charge carriers at the g-CN/water interface, which shows a strong correlation to bond re-forming. A three-step photoreaction mechanism is proposed, whereas the key roles of hole-driven hydrogen transfer and interfacial water configurations were identified. Immediately following photocatalytic water splitting, atomic pathways for the two dissociated hydrogen atoms approaching each other and forming the H gas molecule are demonstrated, while the remanent OH radicals may form intermediate products (e.g., HO). These results provide critical new insights for the characterization and further development of efficient water-splitting photocatalysts from a dynamic perspective.
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http://dx.doi.org/10.1021/acs.nanolett.1c01187DOI Listing
August 2021

Effect of the traditional Chinese medicine Pinggan-Qianyang decoction on SIRT1-PTEN signaling in vascular aging in spontaneously hypertensive rats.

Hypertens Res 2021 Sep 29;44(9):1087-1098. Epub 2021 Jun 29.

International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.

Age-related functional decline is a physiological phenomenon that occurs in all organ systems. However, the acceleration and early occurrence of this process are observed in cardiovascular pathologies, including hypertension. This study aimed to investigate SIRT1-PTEN signaling in aortic tissue from spontaneously hypertensive rats (SHRs) and changes in SIRT1 and PTEN expression following treatment with Pinggan-Qianyang decoction (PGQYD) and explore the mechanism involved in the treatment of hypertensive vascular aging with traditional Chinese medicine. In this study, we used two rat models: spontaneously hypertensive rats (SHRs) at 14 and 64 weeks of age and WKY rats at 64 weeks of age. The degree of irritability and rotation tolerance time were evaluated to determine the effects of PGQYD on animal behavior. The morphology of the thoracic aorta was examined by hematoxylin-eosin (HE) and Masson staining and electron microscopy. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and superoxide dismutase (SOD) and anti-superoxide anion content were detected. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to observe the thoracic aorta during vascular aging. RT-qPCR, immunofluorescence, and Western blot analysis were performed to detect changes in the mRNA and protein expression of p53, p21, SIRT1, and PTEN in rat aortic tissues. Behavioral tests and histological and morphological analyses showed the remarkable amelioration of vascular aging after PGQYD treatment compared with that in the older SHRs. Moreover, PGQYD significantly decreased vascular aging in SHRs, as indicated by reduced SA-β-Gal staining, NADPH oxidase activity, and p53 and p21 expression, and increased anti-superoxide anion and SOD content. Furthermore, PGQYD increased SIRT1 and PTEN expression, but the downregulated expression of SIRT1 induced by a SIRT1 inhibitor abolished the PGQYD-induced antiaging effects on gene expression and antioxidant activity and enhanced PTEN expression. PGQYD could ameliorate vascular aging effects in SHRs, which may have been mediated via the regulation of SIRT1-PTEN signaling in aortic tissue.
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http://dx.doi.org/10.1038/s41440-021-00682-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418988PMC
September 2021

[Progress on in vivo ankle biomechanics based on dual fluoroscopic imaging technology].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Jun;38(3):602-608

Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, P.R. China.

The technical deficiencies in traditional medical imagining methods limit the study of ankle biomechanics. A dual fluoroscopic imaging system (DFIS) provides accurate and non-invasive measurements of dynamic and static activities in joints of the body. This approach can be used to quantify the movement in the single bones of the ankle and analyse different morphological and complex bone positions and movement patterns within these organs and has been widely used in the field of image diagnosis and evaluation of clinical biomechanics. This paper reviews the applications of DFIS that were used to measure the kinematics of the ankle in the field of clinical and sports medicine. The advantages and shortcomings of DFIS in the practical application are summarised. We further put forward effective research programs for understanding the movement as well as injury mechanism of the ankle , and provide constructive research direction for future study.
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http://dx.doi.org/10.7507/1001-5515.202006009DOI Listing
June 2021

Pathological methamphetamine exposure triggers the accumulation of neuropathic protein amyloid-β by inhibiting UCHL1.

Neurotoxicology 2021 Sep 24;86:19-25. Epub 2021 Jun 24.

School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Methamphetamine (METH), a powerful psychoactive drug, causes damage to the nervous system and leads to degenerative changes similar to Alzheimer's disease (AD), however, the molecular mechanism between the toxicity of METH and AD-related symptoms remains poorly understood. In this study, we investigated the effect of METH exposure on the accumulation of amyloid-β by establishing the animal and cell models. The results showed that METH exposure increased amyloid precursor protein (APP) and β-secretase (BACE1), contributed to the accumulation of amyloid-β, and which was alleviated with the pretreatment of BACE1 inhibitor. In addition, METH exposure decreased ubiquitin carboxy-terminal hydrolases L1 (UCHL1) which was related to the degradation of BACE1, and therefore led to the up-regulation of BACE1. In summary, the study could provide a new insight into the molecular mechanisms of METH toxicity and new evidence for the link between METH abuse and AD.
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http://dx.doi.org/10.1016/j.neuro.2021.06.004DOI Listing
September 2021

Clinical study on the safety, efficacy, and prognosis of molecular targeted drug therapy for advanced gastric cancer.

Am J Transl Res 2021 15;13(5):4704-4711. Epub 2021 May 15.

The Third Department of General Surgery, Cangzhou Central Hospital Cangzhou, Hebei Province, China.

Objective: To investigate the safety, efficacy, and prognosis of advanced gastric cancer patients treated with molecular targeted drug therapy.

Methods: A total of 200 patients with metastatic gastric cancer admitted to our hospital from March 2018 to December 2018 were randomly selected and divided into the control group, group A, group B and group C, with 50 patients in each group. Patients in the control group received surgical treatment combined with conventional chemotherapy. Patients in group A were provided with surgical treatment combined with bevacizumab, patients in group B received surgical treatment combined with apatinib, and patients in group C received surgical treatment combined with recombinant human endostatin (RHE). Clinical efficacy, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) levels, Response Evaluation Criteria in Solid Tumors (RECIST), sentinel lymph node (SLD) metastasis, and adverse reactions were compared among different groups of patients with metastatic gastric cancer.

Results: There were no significant differences in treatment efficiency, VEGF and VEGFR-2 levels, RECIST, SLD metastasis value and adverse reactions among group A, group B and group C, and the results were not statistically significant (P>0.05). The levels of VEGF, VEGFR-2, SLD metastasis, and adverse reactions in group A, B, and C were significantly lower than those in the control group (P<0.05). The effective rate of treatment and RECIST in group A, B and C were significantly higher than those in the control group, and the comparison results were statistically significant (P<0.05).

Conclusion: Molecular targeted drug therapy is effective and safe in patients with advanced gastric cancer, and the prognosis of patients is satisfactory, without the proliferation and metastasis of cancer cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205802PMC
May 2021

Identification of macrophage related gene in colorectal cancer patients and their functional roles.

BMC Med Genomics 2021 Jun 13;14(1):159. Epub 2021 Jun 13.

Engineering Research Center for Medicine, Harbin University of Commerce, Harbin, 150076, China.

Background: Recent scientific research has enabled the identification of macrophages related-genes (MaRG), which play a key role in the control of the immune microenvironment in many human cancers. However, the functional role of MaRGs in human tumors is ill-defined. Herein, we aimed at bioinformatically exploring the molecular signatures of MaRGs in colorectal cancer.

Methods: A list of MaRGs was generated and their differential expression was analyzed across multiple datasets downloaded from the publicly available functional genomics database Gene Expression Omnibus. The weighted gene co-expression network analysis (WGCNA) was also applied to identify the partner genes of these MaRGs in colorectal cancer.

Results: After integration of the results from analyses of different datasets, we found that 29 differentially expressed MaRGs (DE-MaRGs) could be considered as CRC-related genes as obtained from the WGCNA analysis. These genes were functionally involved in positive regulation of DNA biosynthetic process and glutathione metabolism. Protein-protein interaction network analysis indicated that PDIA6, PSMA1, PRC1, RRM2, HSP90AB1, CDK4, MCM7, RFC4, and CCT5 were the hub MaRGs. The LASSO approach was used for validating the 29 MaRGs in TCGA-COAD and TCGA-READ data and the results showed that ten among the 29 genes could be considered as MaRGs significantly involved in CRC. The maftools analysis showed that MaRGs were mutated at varying degrees. The nomogram analysis indicated the correlation of these MaRGs with diverse clinical features of CRC patients.

Conclusions: Conclusively, the present disclosed a signature of MaRGs as potential key regulators involved in CRC pathogenesis and progression. These findings contribute not only to the understanding of the molecular mechanism of CRC pathogenesis but also to the development of adequate immunotherapies for CRC patients.
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http://dx.doi.org/10.1186/s12920-021-01010-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201885PMC
June 2021

High frequency ultrasound-guided pericardiocentesis performed in the sitting position: A novel apical approach.

Clin Cardiol 2021 Aug 8;44(8):1106-1112. Epub 2021 Jun 8.

Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China.

Background: So far, few approaches have been described to reduce inadvertent injury to structure of the heart and nearby organs in percutaneous pericardiocentesis.

Hypothesis: We hypothesized that an in-plane high frequency ultrasound-guided apical approach, performed in the sitting position, would provide additional benefits in terms of feasibility and safety for draining malignant pericardial effusion (MPE).

Methods: The authors selected 53 consecutive patients with moderate or large symptomatic MPE who underwent high frequency ultrasound-guided pericardiocentesis. After the procedure, all patients were followed for 90 days with the main purpose of detecting procedure success, procedure-related complications, and recurrent PE.

Results: Procedure success rate for pericardiocentesis was 100%. All patients were placed in the sitting position with their left hands extended above the heads. An apical puncture approach was performed in all cases (100%). The mean duration of catheter drainage was 8.1 ± 3.2 days. The mean initial amount of pericardial fluid drained was 956.3 ± 687.5 ml. Overall, six patients (11%) had recurrent PE; 3 (6%) had repeated percutaneous pericardiocentesis. There was no major complication and minor complications occurred in four patients (8%).

Conclusion: This novel in-plane high frequency US-guided apical approach has several advantages for percutaneous pericardiocentesis of MPE: performed in the sitting position; a benefit for patients with orthopnea; a maximum inserted wide angle to prevent damage to the myocardium; local enlargement of the PE region; high procedure success rate of pericardiocentesis; and excellent clinical outcomes.
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http://dx.doi.org/10.1002/clc.23657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364732PMC
August 2021

Pinocembrin ameliorates arrhythmias in rats with chronic ischaemic heart failure.

Ann Med 2021 12;53(1):830-840

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Objective: Ventricular arrhythmias (VAs) are a common complication of chronic ischaemic heart failure (CIHF). The purpose of this study is to investigate the efficacy of pinocembrin in a rat model of VAs induced by CIHF and further examine the possible mechanism.

Methods: Rats were subjected to ligation of left anterior descending coronary artery to mimic CIHF and then received pinocembrin treatment daily for 2 months. The vivo electrophysiology were performed to determine the effect of pinocembrin on ventricular electrical activity. The expression of Cav1.2, Kv4.2, and NGF was determined by Western blot. The structural change of ventricle was tested by the Echocardiography, Masson staining, and HE staining. The effect of pinocembrin on sympathetic nerve-related markers was detected by the immunostaining and the ELISA was used to test for biomarkers associated with heart failure.

Results: Pinocembrin increased the expression of ion channel protein Cav1.2 and Kv4.3, ameliorated the shortening of action potential duration (APD) and reduced the incidence and duration of ventricular fibrillation (VF). Pinocembrin also reduced the expression of nerve growth factor (NGF) and improved the autonomic nerve remodelling. In addition, pinocembrin reduced the area of infarct area and myocardial fibrosis, accompanied by increasing the expression of connexin protein 43 (C43).

Conclusion: We demonstrate that pinocembrin reduces cardiac nerve remodelling and protects against Vas induced by CIHF. The findings suggest that pinocembrin can be a promising candidate for the treatment of VAs.
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http://dx.doi.org/10.1080/07853890.2021.1927168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172224PMC
December 2021

Corrigendum: Pinocembrin Decreases Ventricular Fibrillation Susceptibility in a Rat Model of Depression.

Front Pharmacol 2021 4;12:647320. Epub 2021 May 4.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

[This corrects the article DOI: 10.3389/fphar.2020.547966.].
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http://dx.doi.org/10.3389/fphar.2021.647320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129570PMC
May 2021

MR T1 mapping for quantifying brain manganese deposition in type C hepatic encephalopathy rats.

Biometals 2021 Aug 29;34(4):841-854. Epub 2021 Apr 29.

Department of Radiology, Jinshan Hospital of Fudan University, 1508 Longhang Road, Shanghai, 201508, China.

To evaluate magnetic resonance (MR) T1 mapping for quantifying brain manganese (Mn) deposition in type C hepatic encephalopathy (CHE) rats and to investigate the mechanism of magnesium sulfate (MgSO) therapy. Thirty Sprague-Dawley rats were randomly assigned into normal control group (NC, n = 6) and CHE groups (n = 24). Thioacetamide (TAA) was used for modeling CHE rats. CHE groups were further divided into 4 subgroups: TAA group, MgSO low dose (Mg-L) group, MgSO high dose (Mg-H) group and deionized water (DW) group (n = 6 for each group). TAA, Mg-L, Mg-H and DW groups were received intraperitoneal injections of 250 mg TAA/kg, twice a week for 8 weeks. Mg-L and Mg-H groups were orally received MgSO of 124 and 248 mg/kg daily, respectively, for another 8 weeks (without TAA). MR T1 mapping was performed in NC, TAA, Mg-L, Mg-H and DW groups at various time points. T1 value and Mn content in basal ganglia, hippocampus, cerebral cortex and cerebellum were evaluated. Morris water maze (MWM) and narrow beat test (NBT) were utilized to evaluate rats' learning, memory and motor ability. Contents of interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a) and calcium-binding adaptor 1 protein (Iba1) were evaluated. Reduced T1 values in basal ganglia, hippocampus and cerebral cortex (P < 0.01, P < 0.05 and P < 0.05, respectively); increased Mn content in basal ganglia, hippocampus and cerebral cortex (all P < 0.05); reduced times of head contacting with region of interest (ROI), reduced times of entrance into the target quadrant (both P < 0.05); increased NBT total time (P < 0.05); increased brain contents of IL-6 (P < 0.001), TNF-α (P < 0.01) and over-expression of Iba1 were found in TAA group compared to NC group. After treated by MgSO, increased T1 value and reduced Mn content in basal ganglia, hippocampus and cerebral cortex (all P < 0.01); increased times of head contacting with ROI, increased times of entrance into the target quadrant (both P < 0.05); reduced NBT total time (P < 0.01); reduced brain content of IL-6, TNF-α (both P < 0.05) and reduced expression of Iba1 were found. T1 values were negatively correlated with Mn contents in basal ganglia (r = - 0.834, P < 0.01), hippocampus (r = - 0.739, P < 0.05), cortex (r = - 0.801, P < 0.05) and cerebellum (r = - 0.788, P < 0.05). T1 mapping could quantify brain Mn deposition in CHE rats. MgSO could improve cognition and motor ability of CHE rats by reducing brain Mn deposition, alleviating neurological inflammation and achieve the effective therapy for CHE. Mn may participate in the pathogenesis of CHE through neuroinflammation.
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http://dx.doi.org/10.1007/s10534-021-00311-2DOI Listing
August 2021

Genome sequence, transcriptome, and annotation of rodent malaria parasite Plasmodium yoelii nigeriensis N67.

BMC Genomics 2021 Apr 26;22(1):303. Epub 2021 Apr 26.

Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, 20892-8132, USA.

Background: Rodent malaria parasites are important models for studying host-malaria parasite interactions such as host immune response, mechanisms of parasite evasion of host killing, and vaccine development. One of the rodent malaria parasites is Plasmodium yoelii, and multiple P. yoelii strains or subspecies that cause different disease phenotypes have been widely employed in various studies. The genomes and transcriptomes of several P. yoelii strains have been analyzed and annotated, including the lethal strains of P. y. yoelii YM (or 17XL) and non-lethal strains of P. y. yoelii 17XNL/17X. Genomic DNA sequences and cDNA reads from another subspecies P. y. nigeriensis N67 have been reported for studies of genetic polymorphisms and parasite response to drugs, but its genome has not been assembled and annotated.

Results: We performed genome sequencing of the N67 parasite using the PacBio long-read sequencing technology, de novo assembled its genome and transcriptome, and predicted 5383 genes with high overall annotation quality. Comparison of the annotated genome of the N67 parasite with those of YM and 17X parasites revealed a set of genes with N67-specific orthology, expansion of gene families, particularly the homologs of the Plasmodium chabaudi erythrocyte membrane antigen, large numbers of SNPs and indels, and proteins predicted to interact with host immune responses based on their functional domains.

Conclusions: The genomes of N67 and 17X parasites are highly diverse, having approximately one polymorphic site per 50 base pairs of DNA. The annotated N67 genome and transcriptome provide searchable databases for fast retrieval of genes and proteins, which will greatly facilitate our efforts in studying the parasite biology and gene function and in developing effective control measures against malaria.
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http://dx.doi.org/10.1186/s12864-021-07555-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072299PMC
April 2021

Effects of dual tasks on kinematic and kinetic performances during stair descent: Respective effects of manual and cognitive tasks.

J Sports Med Phys Fitness 2021 Apr 19. Epub 2021 Apr 19.

Shandong Sport University, Jinan, China -

Background: Stair descent is one of the most common and challenging daily activities for several populations, particularly under dual-task conditions. This study investigated the effects of cognitive or manual task on kinematics and kinetics during stair descent.

Methods: A total of 37 participants performed stair descent under three conditions: stair descending only, stair descending while performing a cognitive task and stair descending while performing a manual task. Kinematic and kinetic data were collected. Multivariate analysis of variance with repeated measures was conducted to test the significant differences among the three conditions.

Results: The gait performance, loading rate, lower limb joint moments and powers were significantly lower under the two dual-task conditions compared with stair descending only. The participants had lower knee flexion/extension range of motion, loading rate, peak hip flexion moment, first peak knee extensor moment, second peak ankle plantar flexion moment, first knee power absorption and less stride width under the manual task compared with the cognitive task.

Conclusions: Dual tasks during stair descent had a significant impact on the kinematics and kinetics of motion, and the effect was more significant while performing a concurrent manual task in healthy young adults. Further studies could focus on the complexity level of dual tasks on the biomechanical parameters during stair walking.
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http://dx.doi.org/10.23736/S0022-4707.21.12204-2DOI Listing
April 2021

Methamphetamine exposure induces neuronal programmed necrosis by activating the receptor-interacting protein kinase 3 -related signalling pathway.

FASEB J 2021 05;35(5):e21561

School of Forensic Medicine, Southern Medical University, Guangzhou, P.R. China.

Methamphetamine (METH) is a synthetic drug with severe neurotoxicity, however, the regulation of METH-induced neuronal programmed necrosis remains poorly understood. The aim of this study was to identify the molecular mechanisms of METH-induced neuronal programmed necrosis. We found that neuronal programmed necrosis occurred in the striatum of brain samples from human and mice that were exposed to METH. The receptor-interacting protein kinase 3 (RIP3) was highly expressed in the neurons of human and mice exposed to METH, and RIP3-silenced or RIP1-inhibited protected neurons developed neuronal programmed necrosis in vitro and in vivo following METH exposure. Moreover, the RIP1-RIP3 complex causes cell programmed necrosis by regulating mixed lineage kinase domain-like protein (MLKL)-mediated cell membrane rupture and dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Together, these data indicate that RIP3 plays an indispensable role in the mechanism of METH-induced neuronal programmed necrosis, which may represent a potential therapeutic target for METH-induced neurotoxicity.
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http://dx.doi.org/10.1096/fj.202100188RDOI Listing
May 2021

Polyglycoside Ameliorated TNBS-Induced Colitis in Rats via Regulating Th17/Treg Balance in Intestinal Mucosa.

J Inflamm Res 2021 1;14:1243-1255. Epub 2021 Apr 1.

Gastroenterology Department, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, People's Republic of China.

Purpose: To investigate the therapeutic effect of polyglycoside (TWP), a derivative from a Chinese traditional herb, on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, in a model for inflammatory bowel disease (IBD) in rats.

Methods: TWP was administrated to Wistar rats during TNBS-induced colitis to determine its therapeutic effect on active inflammation using the Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), flow cytometry, and Western blotting. Peripheral blood CD4 T-cells were isolated from patients with ulcerative colitis (UC) and incubated with TWP to verify its immune regulation mechanism by qRT-PCR and flow cytometry.

Results: Intragastric administration of TWP attenuated the severity of intestinal inflammation in TNBS-induced rat colitis, characterized by decreased DAI, histopathological scores, and expression of IL-6, TNFα, IFNγ, and IL-17A in intestinal mucosa. Furthermore, TWP reduced IL-17ACD4 T-cells, while enhanced Foxp3CD25CD4 T-cells in peripheral blood, mesenteric lymph nodes (MLN), and spleen in rat colitis. Downstream signaling including ROR-γt, STAT3, and HIF1α expression in intestinal mucosa were suppressed by TWP. In addition, incubation with TWP suppressed IL-17ACD4 T-cell differentiation, while it promoted Foxp3CD25CD4 T-cell differentiation in CD4 T-cells isolated from UC patients.

Conclusion: TWP successfully ameliorated experimental rat colitis via regulating innate immune responses as well as Th17/Treg balance in intestinal mucosa, peripheral blood, MLN, and spleen. Moreover, the differentiation of peripheral blood CD4 T-cell isolated from patients with UC was modulated by TWP. TWP may act as an optional complementary and alternative medicine for IBD.
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http://dx.doi.org/10.2147/JIR.S293961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021269PMC
April 2021

Pinocembrin alleviates lipopolysaccharide-induced myocardial injury and cardiac dysfunction in rats by inhibiting p38/JNK MAPK pathway.

Life Sci 2021 Jul 26;277:119418. Epub 2021 Mar 26.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China. Electronic address:

Aim: Recent studies have shown that, with its excellent anti-inflammatory and antioxidant effects, pinocembrin can reduce the occurrence of arrhythmia in myocardial infarction rats. However, whether it can alleviate lipopolysaccharide (LPS)-induced myocardial injury in rats has not been reported. Therefore, the purpose of this study was to investigate whether pinocembrin could alleviate myocardial injury and arrhythmia in rats with sepsis.

Materials And Methods: Rats were intraperitoneally injected with LPS to simulate animal sepsis, and the caudal vein was injected with pinocembrin or normal saline for intervention. Transthoracic echocardiography, inflammatory factors, electrophysiological recording, histological analysis, and western-blot analysis were performed.

Key Findings: Compared with the control group, the rats in the LPS group had myocardial injury and cardiac dysfunction, and the incidence of ventricular arrhythmia increased. In addition, LPS resulted in the increase of p-c-Jun N-terminal kinase (JNK), p-p38 proteins in the myocardium, the levels of inflammatory factors in the blood and the apoptosis rate of left ventricular cardiomyocytes. And all these adverse effects were eliminated, thus confirming that pinocembrin has an excellent protective effect on the heart.

Significance: Reducing the inflammatory response and cell apoptosis by inhibiting p38/JNK mitogen-activated protein kinase (MAPK) signaling pathway, pinocembrin can alleviate myocardial injury, cardiac dysfunction, and ventricular arrhythmia induced by LPS.
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http://dx.doi.org/10.1016/j.lfs.2021.119418DOI Listing
July 2021

Effects of a 16-week Tai Chi intervention on cutaneous sensitivity and proprioception among older adults with and without sensory loss.

Res Sports Med 2021 Jul-Aug;29(4):406-416. Epub 2021 Mar 28.

College of Sports and Health, Shandong Sport University, Jinan, China.

This study investigated the effects of a 16-week Tai Chi (TC) intervention on cutaneous sensitivity and proprioception among older adults with and without sensory loss. Thirty-six older adults were divided into sensory loss and control groups, and they underwent a 16-week TC intervention. Significant interactions were detected in heel cutaneous sensitivity ( = 0.046, = 4.419) and knee flexion ( = 0.043, = 4.580), extension ( = 0.027, = 5.529) and ankle plantar-flexion proprioception ( = 0.037, = 4.860). The post hoc test indicated that in the sensory loss group, heel cutaneous sensitivity threshold ( = 0.034) and knee flexion ( = 0.004), extension ( = 0.002) and ankle plantar-flexion ( = 0.023) proprioception threshold decreased at week 17, whereas in the control group, knee flexion ( = 0.029) proprioception threshold decreased at week 17. TC intervention improved cutaneous sensitivity at more sites and proprioception in more joints among the older adults with sensory loss. TC intervention is a good option for older adults to exercise, and it is more effective among older adults with sensory loss.
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http://dx.doi.org/10.1080/15438627.2021.1906673DOI Listing
June 2021

KCNJ5 Mutation Contributes to Complete Clinical Success in Aldosterone-Producing Adenoma: A Study From a Single Center.

Endocr Pract 2021 Jul 19;27(7):736-742. Epub 2021 Jan 19.

Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China; Laboratory for Endocrine & Metabolic Diseases of Institute of Health Science, Shanghai Jiaotong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, P. R. China. Electronic address:

Objective: The KCNJ5 mutation is the most frequent mutation in aldosterone-producing adenoma (APA). We aimed to illustrate the relationship between KCNJ5 and prognosis after adrenalectomy as a guide for further treatment.

Methods: Our study included 458 patients with APA. Tumor tissues were screened for somatic mutations in KCNJ5 hot-spot regions. We performed a retrospective analysis to identify correlations between KCNJ5 and clinical outcomes in 334 patients with adrenal venous sampling lateralization.

Results: Somatic KCNJ5 mutations were identified in 324 of 458 patients with APA (70.7%). Compared with the KCNJ5-wild type patients, patients with KCNJ5 mutations were younger, had a higher proportion of women, and had shorter durations of hypertension, lower body mass indexes (BMIs), and lower systolic blood pressure values (P < .05). During follow-up, among the 334 patients with APA with adrenal venous sampling lateralization, 320 (95.8%) presented complete biochemical success and 187 (56.0%) presented complete clinical success. One hundred eighty-seven patients with primary aldosteronism who achieved complete clinical success presented the following characteristics: age <40 years (78.7%), BMI <24 kg/m (71.0%), hypertension duration <5 years (78.4%), females (66.9%), and KCNJ5 mutation (65.5%). A multivariate logistic regression analysis identified BMI, hypertension duration, and KCNJ5 mutation as independent predictors of complete clinical success.

Conclusion: The prevalence of KCNJ5 mutations was 70.7%. KCNJ5 mutation is a protective factor of complete clinical success, while BMI and hypertension duration were risk factors of incomplete clinical success.
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http://dx.doi.org/10.1016/j.eprac.2021.01.007DOI Listing
July 2021

sensitizes ovarian cancer cells to irradiation by inhibiting and attenuating autophagy.

Mol Ther Nucleic Acids 2021 Mar 3;23:1110-1119. Epub 2020 Dec 3.

Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081 Heilongjiang Province, China.

Ovarian cancer (OC) is a type of cancer with high prevalence and shocking mortality in women around the world. Radioresistance is a major reason for OC relapse. Mounting studies have shown the significant function of dysregulated microRNAs (miRNAs) in cancer progression and the cellular response to irradiation. The present study inquired about the function and mechanism of microRNA () in regulating radiosensitivity of OC cells. Results showed that was downregulated in OC, and a low level indicated a disappointing prognosis for OC patients. Besides, in OC cells exposed to irradiation, the expression of decreased over time. Functionally, the upregulation of retarded OC cell proliferation and sensitized OC cells to irradiation. Mechanistically, targeted and inhibited fused in sarcoma (). Additionally, was upregulated in OC and its expression further elevated in OC cells under irradiation. Furthermore, targeted to inhibit autophagy, therefore sensitizing OC cells to irradiation. Collectively, our study uncovered as a novel radiosensitizer by targeting in OC cells, which may shed a new light on developing targets for treating patients with OC, particularly those with radioresistance.
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http://dx.doi.org/10.1016/j.omtn.2020.11.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901029PMC
March 2021

Comparative transcriptomic analysis revealed novel potential therapeutic targets of traditional Chinese medicine (Pinggan-Qianyang decoction) on vascular remodeling in spontaneously hypertensive rats.

Chin Med 2021 Feb 10;16(1):21. Epub 2021 Feb 10.

Department of International Medical Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Kaifu District, Changsha, 410008, China.

Background: Both experimental and clinical studies have revealed satisfactory effects with the traditional Chinese formula Pinggan Qianyang decoction (PGQYD) for improving vascular remodeling caused by essential hypertension. The present study explored various therapeutic targets of PGQYD using mRNA transcriptomics.

Methods: In this study, rats were randomly divided into three groups: Wistar-Kyoto (WKY; normal control), spontaneously hypertensive (SHR), and PGQYD-treated rat groups. After 12 weeks of PGQYD treatment, behavioral tests were employed and the morphology of thoracic aortas were examined with hematoxylin-eosin (HE) and Masson staining and electron microscopy. The mRNA expression profiles were identified with RNA-Seq and quantitative real-time PCR to validate changes in gene expression observed with microarray analysis. The gene ontology and pathway enrichment analyses were carried out to predict gene function and gene co-expressions. Pathway networks were constructed to identify the hub biomarkers, which were further validated by western blotting and immunofluorescence analysis.

Results: After PGQYD treatment, the behavioral tests and histological and morphological findings of vascular remodeling were obviously meliorated compared with the SHR group. In the rat thoracic aorta tissues, 626 mRNAs with an exact match were identified. A total of 129 of mRNAs (fold change > 1.3 and P-value < 0.05) were significantly changed in the SHR group compared to the WKY group. Among them, 16 mRNAs were markedly regulated by PGQYD treatment and validated with quantitative real-time PCR. Additionally, target prediction and bioinformatics analyses revealed that these mRNAs could play therapeutic roles through biological processes for regulating cell metabolic processes (such as glycation biology), biological adhesions, rhythmic processes, and cell autophagy. The cellular signaling pathways involved in autophagy may be AGE-RAGE/PI3K/Akt/mTOR signaling pathway.

Conclusion: The present study provides novel insights for future investigations to explore the mechanisms by which PGQYD may effectively inhibit vascular remodeling by activating the AGE-RAGE/PI3K/Akt/mTOR signal pathway in cell autophagy biology.
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http://dx.doi.org/10.1186/s13020-021-00431-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877093PMC
February 2021

CT differentiation of gastric ectopic pancreas from gastric stromal tumor.

BMC Gastroenterol 2021 Feb 4;21(1):52. Epub 2021 Feb 4.

Department of Radiology, TongDe Hospital of ZheJiang Province, No. 234, Gucui Road, Hangzhou, 310012, Zhejiang Province, China.

Background: Gastric ectopic pancreas (GEPs) is a rare developmental anomaly which is difficult to differentiate it from submucosal tumor such as gastric stromal tumor (GST) by imaging methods. Since the treatments of the GEPs and GST are totally different, a correct diagnosis is essential. Therefore, we retrospectively investigated the CT features of them to help us deepen the understanding of GEPs and GST.

Methods: This study enrolled 17 GEPs and 119 GST, which were proven pathologically. We assessed clinical and CT features to identify significant differential features of GEPs from GST using univariate and multivariate analyses.

Results: In univariate analysis, among all clinicoradiologic features, features of age, symptom, tumor marker, location, contour, peritumoral infiltration or fat-line of peritumor, necrosis, calcification, CT attenuation value of unenhancement phase/arterial phase/portal venous phase (CTu/CTa/CTp), the CT attenuation value of arterial phase/portal venous phase minus that of unenhanced phase (DEAP/DEPP), long diameter (LD), short diameter (SD) were considered statistically significant for the differentiation of them. And the multivariate analysis revealed that location, peritumoral infiltration or fat-line of peritumor, necrosis and DEPP were independent factors affecting the identification of them. In addition, ROC analysis showed that the test efficiency of CTp was perfect (AUC = 0.900).

Conclusion: Location, the presence of peritumoral infiltration or fat-line of peritumor, necrosis and DEPP are useful CT differentiators of GEPs from GST. In addition, the test efficiency of CTp in differentiating them was perfect (AUC = 0.900).
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http://dx.doi.org/10.1186/s12876-021-01617-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860050PMC
February 2021
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